1. Field of the Invention
This invention relates to a process for preparing N-substituted amino acid esters. More particularly, it relates to an asymmetric synthetic method for preparing N-substituted .alpha.-amino acids from .alpha.-amino acid esters and .alpha.-substituted carboxylic acid esters.
2. Description of the Prior Art
Some N-substituted amino acid esters are useful as intermediates for the synthesis of various amino acid derivatives which show inhibitory action on angiotensin-transformation enzyme and hence can be used as antidepressants and also are useful as various physiologically active substances such as amavadin, histopine and octopine of natural origins.
(S,S)-N-substituted amino acid esters have been prepared e.g., by reacting (S)-.alpha.-amino acid esters with an equimolar amount of .alpha.-halocarboxylic acid esters in the presence of sodium carbonate and in an organic solvent such as dimethyl formamide. The yields however were not satisfactory, in the order of e.g., 46%, based upon theoretical yield of (S,S)-diasteroisomer (see U.S. Pat. No. 4,542,234). Similarly, methods to conduct these syntheses in organic solvents are also known [see U.S. Pat. No. 4,344,949, U.S. Pat. No. 4,596,791 and Japanese Unexamined Patent Publication No. Sho 60(1985)-13715].
N-Substituted amino acid esters also have been prepared by the reaction of amino acid esters with trifluoro-methyl-sulfonyloxy substituted carboxylic acid esters in the presence of triethylamine and in an organic solvent such as methylene chloride, with high yield (see DE 3,303,344, Japanese Unexamined Patent Publication No. Sho 59(1984)-172442).
It has been reported that in the preparation of N-substituted amino acid esters from amino acid esters and .alpha.-halo carboxylic esters, .alpha.-tosyloxy carboxylic acid esters or .alpha.-mesyloxy carboxylic acid esters, silber ion catalyst was required to achieve high yield (see U.S. Pat. No. 4,350,704).
In such known methods, all the reactions are conducted in a homogeneous system using organic solvents and do not afford a sufficient yield unless carboxylic acid esters having very strong active trifluorosulfonyloxy group or silber ion catalyst are used. Furthermore carboxylic acid esters having trifluorosulfonyloxy group must be handled with due attention because they are unstable and show a tearing property. Accordingly, it is desired to develop a method for the preparation of N-substituted amino acid esters in high yield which can be easily treated and conducted under conditions which are not severe.
Thus, the inventors have found an efficient asymmetric synthetic method for preparing N-substituted amino acid esters which is conducted in the absence of solvent and affords a good yield.